Cornus mas and Cornus officinalis—A Comparison of Antioxidant and Immunomodulatory Activities of Standardized Fruit Extracts in Human Neutrophils and Caco-2 Models

Abstract

Fruits of Cornus mas and Cornus officinalis are representative plant materials traditionally used in Europe and Asia, respectively, in the treatment of diabetes and diabetes-related complications, which are often mediated by pathogenic inflammatory agents. Additionally, due to the fact of mutual infiltration of Asian and European medicines, the differentiation as well as standardization of traditional prescriptions seem to be crucial for ensuring the quality of traditional products. The objective of this study was a comparison of biological activity of extracts from fruits of C. mas and C. officinalis by an assessment of their effect on reactive oxygen species (ROS) generation in human neutrophils as well as cytokines secretion both in neutrophils (tumor necrosis factor α, TNF- α; interleukin 8, IL-8; interleukin 1β, IL-1β) and in human colon adenocarcinoma cell line Caco-2 (IL-8). To evaluate the phytochemical differences between the studied extracts as well as to provide a method for standardization procedures, a quantitative analysis of iridoids, such as loganin, sweroside, and loganic acid, found in extracts of Cornus fruits was performed with HPLC-DAD. All standardized extracts significantly inhibited ROS production, whereas the aqueous-alcoholic extracts were particularly active inhibitors of IL-8 secretion by neutrophils. The aqueous-methanolic extract of C. officinalis fruit, decreased IL-8 secretion by neutrophils to 54.64 ± 7.67%, 49.68 ± 6.55%, 50.29 ± 5.87% at concentrations of 5, 50, and 100 µg/mL, respectively, compared to LPS-stimulated control (100%). The aqueous extract of C. officinalis fruit significantly inhibited TNF-α release by neutrophils at concentrations of 50 and 100 µg/mL. On the other hand, the aqueous-ethanolic extract of C. mas fruit showed the propensity to increase TNF-α and IL-1β secretion. The modulatory activity of the Cornus extracts was noted in the case of secretion of IL-8 in Caco-2 cells. The effect was comparable with dexamethasone. The content of loganin in aqueous and aqueous-methanolic extract of C. officinalis fruit was higher than in the aqueous-ethanolic extract of C. mas fruit, which was characterized by a significant quantity of loganic acid. In conclusion, the immunomodulatory effect observed in vitro may partially confirm the traditional use of Cornus fruits through alleviation of the development of diabetes-derived inflammatory complications. Loganin and loganic acid are significant markers for standardization of C. mas and C. officinalis fruit extracts, respectively.

Biological Activity of Extracts of Red and Yellow Fruits of Cornus mas L.—An In Vitro Evaluation of Antioxidant Activity, Inhibitory Activity against α-Glucosidase, Acetylcholinesterase, and Binding Capacity to Human Serum Albumin

“…The other constituent components, iridoids and their glycosides, show a wide range of t actions such as cardiovascular, hypoglycemic, hypolipidemic, antioxidant, anti-inflammatory, immunomodulatory action, etc. [ 8 , 31 , 32 ]. Rational use of plant extracts in treatment will be possible if we understand the mechanism of their action on biological systems at the molecular and cellular levels.…”

“…However, the latter includes more iridoids and phenolic acids [ 7 ]. The constituent components of extracts from Cornus mas L. exhibit a variety of biological activities, making the extract a promising compound in the treatment of various diseases, especially gastrointestinal and metabolic disorders, diabetes and diabetes-related complications, stomach ulcers, diarrhea, fever, sore throats, urinary tract infections and liver and kidney diseases [ 8 , 9 ]. Moreover, little is known about the biological effects of extract of yellow fruits of Cornus mas L., in comparison with extract of red fruits of Cornus mas L.…”

“…Despite the widespread use of synthetic compounds [ 10 ], phytotherapy remains a popular subject of scientific research as a source of biologically active compounds with various properties. The principal advantage of natural compounds of plant origin lies in their wide range of action with minimal or no side effects in vivo [ 7 , 8 , 9 ]. Using drugs based on natural compounds in the early stages of the disease can prevent the development of serious complications or improve the condition of patients in the later stages of a disease progression [ 14 , 15 , 16 ].…”

Fruits of Hippophaë rhamnoides in human leukocytes and Caco-2 cell monolayer models—A question about their preventive role in lipopolysaccharide leakage and cytokine secretion in endotoxemia

“…The Caco-2 cells were cultured in DMEM supplemented with 20% FBS (v/v), L-alanyl-L-glutamine (2 mM), penicillin (100 IU/ ml), streptomycin (100 μg/ml), and amphotericin B (2.5 ng/ml). The details of cell culturing were previously described (Czerwińska et al, 2021). Passages between 20 and 45 were used in all in vitro experiments.…”

Potentially Bio-Accessible Metabolites from an Extract of Cornus mas Fruit after Gastrointestinal Digestion In Vitro and Gut Microbiota Ex Vivo Treatment

“…Both cornuside and loganic acid have also been proven to suppress those cytokines’ activity [ 16 , 17 ]. In our previous study, it was shown that in human neutrophils ex vivo and colon adenocarcinoma cell line in vitro cornelian cherry significantly reduced the level of IL-8 [ 18 ], which is a chemoattractant involved in the development of inflammatory process [ 19 ]. Furthermore, according to clinical data, the consumption of C. mas extract resulted in a decrease of highly sensitive C-reactive protein (hsCRP) in postmenopausal women [ 20 ].…”